Generation of Hepatic Stellate Cells from Human Pluripotent Stem Cells Enables In Vitro Modeling of Liver Fibrosis
| Autor: | Ayla Smout, Adil El Taghdouini, Inge Mannaerts, Ruben Boon, Leo A. van Grunsven, Isabel Graupera, Beatriz Aguilar-Bravo, Daniel Rodrigo-Torres, Juan José Lozano, Christophe Chesne, Pau Sancho-Bru, Catherine M. Verfaillie, Etienne Sokal, Julia Vallverdú, Delia Blaya, L. Perea, Mar Coll, Sofia B. Leite, Mustapha Najimi |
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| Přispěvatelé: | Basic (bio-) Medical Sciences, Liver Cell Biology, Faculty of Medicine and Pharmacy, Translational Liver Cell Biology, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Liver Cirrhosis
Male 0301 basic medicine Thioacetamide HEPATOCYTES non-parenchymal cells Lipid droplet disease modeling toxicity assessment Induced pluripotent stem cell SPECIFICATION organoids Cells Cultured liver fibrosis DEFINITIVE ENDODERM liver spheroids Cell Differentiation hemic and immune systems Phenotype 3. Good health Cell biology medicine.anatomical_structure DIFFERENTIATION Hepatocyte Molecular Medicine Female Life Sciences & Biomedicine Pluripotent Stem Cells EXPRESSION Cell type Biology Models Biological 03 medical and health sciences Cell & Tissue Engineering REGENERATION Hepatic Stellate Cells Journal Article Genetics medicine INJURY Humans in vitro liver model Wound Healing Science & Technology RECEPTOR Infant Newborn Cell Biology Coculture Techniques In vitro 030104 developmental biology MARKER Hepatic stellate cell Wound healing COMMITMENT |
| Zdroj: | Cell Stem Cell Cell stem cell, Vol. 23, no.1, p. 101-113.e7 (2018) |
| Popis: | The development of complex in vitro hepatic systems and artificial liver devices has been hampered by the lack of reliable sources for relevant cell types, such as hepatic stellate cells (HSCs). Here we report efficient differentiation of human pluripotent stem cells into HSC-like cells (iPSC-HSCs). iPSC-HSCs closely resemble primary human HSCs at the transcriptional, cellular, and functional levels and possess a gene expression profile intermediate between that of quiescent and activated HSCs. Functional analyses revealed that iPSC-HSCs accumulate retinyl esters in lipid droplets and are activated in response to mediators of wound healing, similar to their in vivo counterparts. When maintained as 3D spheroids with HepaRG hepatocytes, iPSC-HSCs exhibit a quiescent phenotype but mount a fibrogenic response and secrete pro-collagen in response to known stimuli and hepatocyte toxicity. Thus, this protocol provides a robust in vitro system for studying HSC development, modeling liver fibrosis, and drug toxicity screening. ispartof: CELL STEM CELL vol:23 issue:1 pages:101-+ ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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